title: TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury.
abstract: The ankyrin-repeat transient receptor potential 1 (TRPA1) has been implicated in pathological conditions of the bladder, but its role in overactive bladder (OAB) following spinal cord injury (SCI) remains unknown. In this study, using a rat SCI model, we assessed the relevance of TRPA1 in OAB induced by SCI. SCI resulted in tissue damage, inflammation, and changes in bladder contractility and in voiding behavior. Moreover, SCI caused upregulation of TRPA1 protein and mRNA levels, in bladder and in dorsal root ganglion (DRG; L6-S1), but not in corresponding segment of spinal cord. Alteration in bladder contractility following SCI was evidenced by enhancement in cinnamaldehyde-, capsaicin-, or carbachol-induced bladder contraction as well as in its spontaneous phasic activity. Of relevance to voiding behavior, SCI induced increase in the number of nonvoiding contractions (NVCs), an important parameter associated with the OAB etiology, besides alterations in other urodynamic parameters. HC-030031 (TRPA1 antagonist) treatment decreased the number and the amplitude of NVCs while the TRPA1 antisense oligodeoxynucleotide (AS-ODN) treatment normalized the spontaneous phasic activity, decreased the cinnamaldehyde-induced bladder contraction and the number of NVCs in SCI rats. In addition, the cinnamaldehyde-induced bladder contraction was reduced by exposure of the bladder preparations to HC-030031. The efficacy of TRPA1 AS-ODN treatment was confirmed by means of the reduction of TRPA1 expression in the DRG, in the corresponding segment of the spinal cord and in the bladder, specifically in detrusor muscle. The present data show that the TRPA1 activation and upregulation seem to exert an important role in OAB following SCI.
authors.affiliation: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina SC, Brazil.
authors.forename: Edinéia Lemos
authors.initials: EL
authors.lastname: Andrade
authors.forename: Stefânia
authors.initials: S
authors.lastname: Forner
authors.forename: Allisson Freire
authors.initials: AF
authors.lastname: Bento
authors.forename: Daniela Ferraz Pereira
authors.initials: DF
authors.lastname: Leite
authors.forename: Marcos Antonio
authors.initials: MA
authors.lastname: Dias
authors.forename: Paulo César
authors.initials: PC
authors.lastname: Leal
authors.forename: Janice
authors.initials: J
authors.lastname: Koepp
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017487:Ankyrins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D014563:Urodynamics / Q000187:drug effects
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D017487:Ankyrins; D015220:Calcium Channels; D016376:Oligonucleotides, Antisense; D011687:Purines; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D000171:Acrolein; D002217:Carbachol; D002211:Capsaicin; C012843:cinnamaldehyde